Biopharming - Introduction, Application, benefits and potential threats

Biopharming is an upcoming research field related with genetic engineering and biotechnology which is ensuring the future health of the humanity while letting us making so many therapeutics. Also, it let us consume some vaccines as an oral food source, showing some perfect alternative for the developing countries. However, this is yet to be argued, tested and confirmed for its biosafety for both human and to nature.

1. BIOPHARMING
ISURU PRIYARANGA

3. OUTLINE
Definition
Key Millstones
The Process
Animal/ Plant Biopharming-Applications
Advantages and Disadvantages
Ethical Issues
Acknowledgement
References

4. The application of genetic engineering on living
organisms to produce pharmacologicallyactive
substances.
Theproductionofpharmaceuticalsbyusing
geneticallymodifiedplantsoranimals.
DEFINITION
-Segen'sMedical Dictionary (2012)
-McGraw-Hill Dictionary of Scientific &
Technical Terms (2003)

5. Major Categories
Animal
Biopharming
Plant
Biopharming

6. Biopharming(Molecular-pharming)
Vs.
Molecular Farming
What’s Correct ?

7. Key Milestones
•1982 -1
st
transgenic drug, insulinusing
Escherichia colibacteria.
•1990-1
st
GE plant-derivedprotein (PDP) -
Human serum albumin (P. C. Sijmonset al. ,1990)
•1998-1
st
animal-derivedtransgenic protein,
Human Tissue Plasminogen Activator in milk
of mice. (Clark, A.J., 1998)

8. Key Milestones
•2006-1
st
licensing of plant-made vaccine: for
Newcastle diseaseusing tobacco plants
•2009-1
st
licensing of animal-made
pharmaceutical Anticoagulant antithrombin
using GE goat (Heavey, S., 2009)
•2014-Highly suceededZmappvaccine, made
for Ebola virus using tobacco plants.
(Rybicki, E.P. ,2014)

9. The Basic Process
Gene of interest
Suitable
Vector
Plant or Animal
Protein Expression in
Harvest
Biochemical and
Clinical Tests
Extracted products or
Direct consumption
Electric Shock

10. Animal Biopharming
Enables an animal to make a certain
pharmaceutical proteinin its,
Milk
Urine
Blood
Sperm
Eggs
Human Proteins , Vaccines, Monoclonal Antibodies
Ex: Lipase (Sheep, Rabbits)
Growth Hormone (Goats)
Factor VIII (Cattle)

11. The Process
http://www.cas.miamioh.edu/~wil
sonkg/old/gene2005/manipulation
/geneengneering/tools/tools_files/
tech_apps.htm
Source:
Fig. 01 –Animal BiopharmingProcess

12. Animal Biopharming
Source: Goven, J., (2008)
Fig.2 –Detailed table on animal Biopharmingproducts

13. Advantages and Disadvantages
1)Can scale up & Cost reduction-(20-50 $ /g)
2)Complex protein processing
3)Very high expression levels
1)Viral contamination
2)Long time scales
3)Little regulatory experience
Advantages
Disadvantages

14. Plant Biopharming
Enables an plant to make a certain
pharmaceutical molecules for non food,
feed or fiber applications.
Plant-made antibodies (plantibodies)
Plant-made vaccines (edible vaccines)
Plant-made therapeutic proteins and
intermediates

15. 1. Plant-made Antibodies
Source: Ko, K. and Koprowski, H. (2005)
Table 1 –Examples for monoclonal antibodies derived from plants

16. 2. P-M Vaccines (Edible)
Hepatitis virus B surface antigen
-tobacco / potato / lettuse
Newcastle virus disease
-tobacco
Cholera -Rice

17. The Process
Source:Langridge, W. H. R. , (2000)

18. 3. P-M Therapeutic Proteins
Human serum albumin
-potato and tobacco
Human GH produced
-tobacco chloroplast.
Human Lactoferine
-Potato

19. Plant Biopharming
Source: Ahmad, P., et el. (2012) , Gayatonde, V. (2016)
Fig. 4 & 5 –Expression of different antigens/antibodies, proteins in plants.

20. Advantages and Disadvantages
1)Easy scale up & Cost reduction-(10-20$ /g)
2)Stability -Storage
3)Safety -Free from animal Viruses, etc.
4)Shorter development Cycles
1)Environment contamination
2)Food supply contamination
3)Health safety concerns –allergens, field chemicals.
Advantages
Disadvantages

21. Widely Using Plants & The Problem
Elbehri, A., (2005)
2

22. Why we need Biopharming?
Expression
System
Production
Quality
Contam-
ination
Risk
Scale-up
Capacity
Storage
Ability
Time effort
Forthe
process
Ethical
Issues
Production
Cost
Bacteria Low EndotoxinsHigh Medium Low Low Low
Yeast Medium Low High Medium Medium Low Medium
Mammalian
Cell Cultures
Very High Virus,
Oncogenes
VeryLow DifficultHigh Exist High
Plant Cell
Cultures
High Low Medium Medium Medium Low Medium
Transgenic
Animals
Very High Virus,
Oncogenes
Low DifficultHigh Very HighHigh
Transgenic
Plants
High Low High Easy High Exist Low
Source: Biemelt, S. & Sonnewald, U. (2004) , Elbehri, A., (2005)
Table:03 –A comparison of pharmaceutical expression systems

23. Why we need Biopharming?
Elbehri, A., (2005)

24. Suggestions for some Biosafety Issues
GE Methods
Chloroplast transformation
Use completely closed facilities or greenhouses
Use of pharmaplants with a “terminator gene”
Use visual markers for easy identification

25. Suggestions for some Biosafety Issues
Physical Methods
Remove male flowers of GM plant
Use Isolated fields
Use Barrier crops

26. Ethical Issues ?

27. ACKNOWLEDGEMENT
Department of botany,
Faculty of Applied Science,
University of Sri Jayewardenepura.

28. REFERENCES
•Ahmad, P., Ashraf, M., Younis, M., Hu, X., Kumar, A., Akram, N.A. and Al-Qurainy,
F., (2012). Role of transgenic plants in agriculture and biopharming.
Biotechnology advances, 30(3), pp.524-540.
•Barta, A., Sommergruber, K., Thompson, D., Hartmuth, K., Matzke, M.A. and
Matzke, A.J., (1986). The expression of a nopalinesynthase—human growth
hormone chimaericgene in transformed tobacco and sunflower callus tissue.
Plant Molecular Biology, 6(5), pp.347-357.
•Biemelt, S., Tschiersch, H. and Sonnewald, U., (2004). Impact of altered
gibberellin metabolism on biomass accumulation, lignin biosynthesis, and
photosynthesis in transgenic tobacco plants. Plant Physiology, 135(1), pp.254-
265.
•Byrne, P., (2003). Bio-pharming.Crop series. Production; no. 0.307.
•Clark, A.J., (1998). The mammary gland as a bioreactor: expression, processing,
and production of recombinant proteins. Journal of mammary gland biology
and neoplasia, 3(3), pp.337-350.

29. REFERENCES
•Elbehri, A., (2005). Biopharmingand the food system: examining the potential
benefits and risks.
•Fischer, R., Stoger, E., Schillberg, S., Christou, P. and Twyman, R.M., (2004).
Plant-based production of biopharmaceuticals. Current opinion in plant biology,
7(2), pp.152-158.
•Gayatonde, V., Singh, D. K., Reddy, P. S., & Vennela, P. R. (2016). Biopharming–
Making Plants into Factories.Advances in Life Sciences,5(6), 2019-2026.
•Goven, J., Hunt, L.M., Shamy, D. and Heinemann, J.A., (2008). Animal
biopharmingin New Zealand: drivers, scenarios and practical implications.
•Juarez, P., Virdi, V., Depicker, A. and Orzaez, D., (2016). Biomanufacturingof
protective antibodies and other therapeutics in edible plant tissues for oral
applications.Plant biotechnology journal,14(9), pp.1791-1799
•Laere, E., Ling, A.P.K., Wong, Y.P., Koh, R.Y., MohdLila, M.A. and Hussein, S.,
(2016). Plant-based vaccines: Production and challenges.Journal of
Botany,2016.

30. REFERENCES
•Langridge, W.H., (2000). Edible vaccines.SCIENTIFIC AMERICAN-AMERICAN
EDITION-,283(3), pp.48-53.
•Lillydiabetes.com. (2018). Heritage | LillyDiabetes.com. [online] Available at:
http://www.lillydiabetes.com/heritage.aspx [Accessed 20 Jan. 2018].
•QiuX, Wong G, AudetJ, Bello A, Fernando L, AlimontiJB, Fausther-BovendoH,
Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, BohorovO, BohorovaN,
Goodman C, Kim D, PaulyMH, Velasco J, PettittJ, OlingerGG, Whaley K, XuB,
Strong JE, ZeitlinL, KobingerGP, (2014). Reversion of advanced Ebola virus
disease in nonhuman primates with ZMapp. Nature 2014, 514: 47-53.
•Rishi, A.S., Nelson, N.D. and Goyal, A., (2001). Molecular farming in plants: a
current perspective. Journal of Plant Biochemistry and Biotechnology, 10(1),
pp.1-12.
•Rybicki, E.P., (2014). Plant-based vaccines against viruses. Virology journal,
11(1), p.205.

31. REFERENCES
•Sijmons, Peter C.; Dekker, Ben M. M.; Schrammeijer, Barbara; et al. (1990).
"Production of Correctly Processed Human Serum Albumin in Transgenic
Plants". Bio/Technology. 8 (3): 217–21.
•Sijmons, P.C., Dekker, B.M., Schrammeijer, B., Verwoerd, T.C., Van Den Elzen, P.J.
and Hoekema, A., (1990). Production of correctly processed human serum
albumin in transgenic plants. Nature Biotechnology, 8(3), pp.217-221.
•Takeyama, N., Kiyono, H. and Yuki, Y., 2015. Plant-based vaccines for animals
and humans: recent advances in technology and clinical trials.Therapeutic
advances in vaccines,3(5-6), pp.139-154.
•U.S. (2018). U.S. approves first drug from DNA-altered animals. [online]
Available at: https://www.reuters.com/article/us-gtc-atryn/u-s-approves-first-
drug-from-dna-altered-animals-idUSTRE5154OE20090206 [Accessed 22 Jan.
2018].

32. Thank You !
ISURU PRIYARANGA